The tumor necrosis factor type 2 receptor plays a protective role in tumor necrosis factor-α-induced bone resorption lacunae on mouse calvariae

Kenichi Nagano, Neil Alles, Anower Hussain Mian, Asako Shimoda, Nobuyuki Morimoto, Yukihiko Tamura, Hitoyata Shimokawa, Kazunari Akiyoshi, Keiichi Ohya, Kazuhiro Aoki

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF)-α exerts its biological function via TNF type 1 and type 2 receptors (TNFR1 and TNFR2). We have previously reported that bone resorption induced by lipopolysaccharide (LPS) in TNFR2-deficient mice is accelerated compared to that in wild-type (WT) mice. Although these results suggested that TNFR2 might have a protective role in bone resorption, we could not exclude the possibility that TNFR2 has no role in bone resorption. To clarify the role of TNFR2, we developed a TNF-α-induced bone resorption model using cholesterol-bearing pullulan nanogel as a TNF-α carrier to minimize the influence of inflammatory cytokines other than TNF-α. Injections of human TNF-α (hTNF), an agonist of mouse TNFR1, stimulated bone resorption lacunae on the calvariae in WT mice, but mouse TNF-α (mTNF), an agonist of both mouse TNFR1 and TNFR2, could not. To eliminate the possibility that the TNFR1 agonistic effects of hTNF were stronger than those of mTNF, we used the same model in TNFR2-deficient mice. Injection of mTNF resulted in clear bone resorption lacunae to the same extent observed after using hTNF in the TNFR2-deficient mice. Histomorphometric analysis of osteoclast number supported the observed changes in bone resorption lacunae. These data suggest that TNFR2 has a protective role in TNF-α-induced bone resorption.

Original languageEnglish
Pages (from-to)671-681
Number of pages11
JournalJournal of Bone and Mineral Metabolism
Volume29
Issue number6
DOIs
Publication statusPublished - 2011 Nov

Keywords

  • Bone resorption lacunae
  • Cholesterol-bearing pullulan
  • Human TNF-α
  • Mouse TNF-α
  • TNF type 2 receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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